This invention relates to novel nucleoside or nucleotide analogs, processes for their synthesis and incorporation into polynucleotides.
The following is a brief description of nucleoside analogs. This summary is not meant to be complete but is provided only for an understanding of the invention that follows. This summary is not an admission that all of the work described below is prior art to the claimed invention.
Nucleoside modifications of bases and sugars, have been discovered in a variety of naturally occurring RNA (e.g., tRNA, mRNA, rRNA; reviewed by Hall, 1971 The Modified Nucleosides in Nucleic Acids, Columbia University Press, New York; Limbach et al., 1994 Nucleic Acids Res. 22, 2183). In an attempt to understand the biological significance, structural and thermodynamic properties, and nuclease resistance of these nucleoside modifications in nucleic acids, several investigators have chemically synthesized nucleosides, nucleotides and phosphoramidites with various base and sugar modifications and incorporated them into oligonucleotides.
Uhlmann and Peyman, 1990, Chem. Reviews 90, 543, review the use of certain nucleoside modifications to stabilize antisense oligonucleotides.
Usman et al., International PCT Publication Nos. WO/93/15187; and WO 95/13378; describe the use of sugar, base and backbone modifications to enhance the nuclease stability of enzymatic nucleic acid molecules.
Eckstein et al., International PCT Publication No. WO 92/07065 describe the use of sugar, base and backbone modifications to enhance the nuclease stability of enzymatic nucleic acid molecules.
Grasby et al., 1994, Proc. Indian Acad. Sci., 106, 1003, review the "applications of synthetic oligoribonucleotide analogues in studies of RNA structure and function".
Eaton and Pieken, 1995, Annu. Rev. Biochem., 64, 837, review sugar, base and backbone modifications that enhance the nuclease stability of RNA molecules
Mitsunobu, 1981, Synthesis, 1, 1-28, described a process for the conversion of alcohol (ROH) to aminooxy alcohol (RONH.sub.2).
The process descibed by Mitsunobu (supra) has been been applied in the conversion of sugars and disaccharides (Grochowski et al., 1976, 50, C15; Synthesis 1976, 682; J. Bull. Pol. Acad. Sci. Chem. Commun., 1987, 35, 255; Tronchet et al., 1982, Helv. Chim. Acta., 65, 1404; Carbohydr. Res., 1990, 204).
The process descibed by Mitsunobu (supra) has also been applied in the synthesis of 3'-O--3NH.sub.2 nucleosides and 5'-O--NH.sub.2 nucleosides (Nielsen, 1995, Annu. Rev. Biomol. Struc., 24, 167; Burgess et al., 1994, J. Chem. Soc. Chem. Commun., 915; Kondo et al., 1985, Am. Chem. Soc. Symp. Ser., 16, 93; Vasseur et al., 1992, J. Am. Chem. Soc., 114, 4006; Tronchet et al., 1994, 13, 2071; Perbost et al., 1995, J. Org. Chem., 60, 5150).
The references cited above are distinct from the presently claimed invention since they do not disclose and/or contemplate the synthesis of the nucleoside analogs, such as the 2'-O-amino nucleosides of the instant invention.